New Species-Selective Antimicrobials to Thwart Developing Resistance

Case ID:

D2015-58

Web Published:

7/13/2016

Description:

Project ID:D2015-58

IP Status: PCT patent application filed

Invention Description and Novelty: Drug resistance limits the effectiveness of most currently used antimicrobial agents. Infectious organisms are becoming resistant to even the most recently developed antimicrobials that target essential steps in cell wall assembly and protein biosynthesis. Researchers at The University of Toledo have created new antimicrobials with unique modes of action against a new drug target.

Applications: Compounds and methods for developing new antimicrobials that are species-selective and act through a mechanism other than by targeting cell wall biosynthesis or DNA replication.

Value Propositions:

• This amino acid biosynthetic pathway is unique to microbial organisms, with no mammalian homologs. That is, this entire pathway is absent in mammals.

• Structure-guided development of these inhibitor compounds has produced low micromolar inhibitors of the target enzyme, with high selectivity observed between the Gram-negative and Gram-positive bacterial orthologs.

• This family of inhibitor compounds includes the most potent inhibitors that have been identified against the target enzyme.

• Any of these inhibitors can be formulated or administered as prodrugs useful for treating various infections such as, but not limited to, bacterial infections, viral infections, fungal infections, and protozoal infections. The compounds are particularly useful for treatment of infection in patients infected with a multidrug-resistant pathogen including, but are not limited to, Streptococcus pneumoniae; drug-resistant Campylobacter, Neisseria gonorrhoeae, nontyphoidal Salmonella, Shigella; methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum -lactamase (ESBL)-producing Enterobacteriaceae, vancomycin-resistant Enterococcus (VRE), carbapenem-resistant Enterobacteriaceae (CRE), and Clostridium difficile.